The Bees are unbeaten in their last 13 matches, the latest a 3-1 victory over Reading that sees them in fourth place in the EFL Championship table. Newcastle sit 12th in the Premier League table following a 1-1 draw against Fulham.
Brentford are in the EFL Cup quarterfinals for the first time and have knocked out three Premier League clubs in Southampton, West Bromwich Albion and Fulham on their way to the last eight.
Bees manager Thomas Frank revealed that midfielder Christian Norgaard will be in the squad for the first time since October after recovering from an ankle injury. Ethan Pinnock returns from suspension after serving a one-match ban while defender Pontus Jansson remains out with an ankle issue.
Magpies boss Steve Bruce has revealed several key players will miss out due to COVID-19, including defender Federico Fernandez, who was substituted at halftime of Newcastle's last match against Fulham with fatigue with Isaac Hayden set to be the Argentine's stand-in once again.
Jamal Lascelles and Allan Saint-Maximin are still recovering from effects of the virus while backup goalkeeper Martin Dubravka is working his way back from an ankle injury, but is not fit to return. Javi Manquillo, Fabian Schar and Paul Dummett are also doubtful to make the trip to London.
Brentford: Martin; Dalsgaard, Goode, Pinnock, Henry; Dasilva, Janelt, Jensen; Mbeumo, Toney, Canos
Newcastle United: Darlow; Lewis, Clark, Hayden, Murphy; Ritchie, Longstaff, Shelvey, Fraser; Wilson, Carroll
Head to head
The only previous meetings between Brentford and Newcastle came in the 2016/17 season when they matched up in the Championship.
The Magpies were winners on both occasions, claiming a 3-1 victory on October 15th, 2016 at St. James' Park with a brace from Dwight Gayle after Ciaran Clark had opened the scoring. Scott Hogan scored in the 52nd minute for the Bees.
The reverse fixture at Griffin Park saw Gayle again on the scoresheet, giving Newcastle a 20th minute lead before Lasse Vibe leveled in the 52nd minute for the hosts. Daryl Murphy's 79th minute header was the match winner and returned the Magpies to the top of the table.
Ones to watch
Striker Ivan Toney has set the Championship alight after moving from Peterborough United. The former Newcastle man has 15 goals in 18 appearances for Brentford and will be motivated to show his former side what they're missing out on.
Callum Wilson has proved to be an excellent acquisition, leaving AFC Bournemouth following the Cherries relegation from the top flight last season for the Tynesiders, scoring the equalizer against Fulham, his eighth goal of the season.
Frank spoke about Brentford's run so far and the opportunity that awaits them tomorrow.
"If we hit a high level we are very difficult to beat and have a good chance. Now we have done it (beat top-flight sides) three times. We can't we do it the fourth time? We are confident but we are humble because we know we have a massive task in front of us.
"You always want to be a part of history or to write a new chapter in this beautiful club's history. When you have the chance just in front of you, it is so important to give everything you can to take that chance. We believe in our chance and will go for it."
Bruce is urging his players to take this chance as Newcastle seek their first EFL Cup semifinal since the 1975/76 season.
"Once you get to a quarterfinal, there's a semifinal at stake. We haven't been there for years. I hope we're looking forward to it. Certainly I am.
"The games are coming thick and fast, but what an opportunity we've got. We've got a wonderful opportunity to get to the semifinal of the cup, let's look forward to it, enjoy the challenge of it and see where we can go."
How to watch
The match will be available to watch on Sky Sports Main Event and Sky subscribers have the option of viewing the action on their website or app. Kick-off is at 18:30 BST.